Bone Density, Structure, and Estimated Strength in Transgender Youth Receiving Pubertal Suppression in Early Puberty

青春期早期接受青春期抑制的跨性别青少年的骨密度、结构和估计强度

• 批准号: 9756170
• 负责人: Janet Yi Man Lee
• 金额: $ 7.49万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2020-07-02
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9756170
• 关键词: 25-hydroxyvitamin D; Adolescent; Age; Agonist; Area; Attenuated; Biometry; Body Composition; Body measure procedure; Bone Density; Bone Development; Bone Growth; Bone Resorption; C-telopeptide; Caring; Child Care; Childhood; Clinical; Cohort Studies; Complex; Coupled; Data; Data Analyses; Densitometry; Diagnostic radiologic examination; Dietary Calcium; Drops; Dual-Energy X-Ray Absorptiometry; Elderly; Endocrinology; Enrollment; Ensure; Epidemiology; Estradiol; European; Exercise; Fellowship; Fracture; Future; Gender; Goals; Gonadal Steroid Hormones; Gonadotropin Hormone Releasing Hormone; Growth; Guidelines; Health; Hormones; Image; Impairment; Incidence; Insulin-Like Growth Factor I; Intervention; Investigation; K-Series Research Career Programs; Knowledge; Laboratories; Lead; Learning; Life; Measures; Medical; Mental Health; Mentorship; N-terminal; Osteogenesis; Outcome; Participant; Peripheral; Physicians; Physiological; Procollagen; Puberty; Radiology Specialty; Reference Values; Reporting; Research; Resolution; Risk; Scientist; Site; Skeletal Development; Skeletal bone; Skeleton; Structure; Testing; Testosterone; Time; Training; Treatment Protocols; Vitamin D; Weight-Bearing state; Work; X-Ray Computed Tomography; Youth; age related; attenuation; bone; bone age; bone health; bone imaging; bone mass; bone metabolism; bone quality; bone strength; bone turnover; boys; calcium intake; clinical care; clinical practice; design; diet and exercise; experience; fracture risk; gender dysphoria; gender nonconforming; girls; hormone therapy; improved; intervention effect; lean body mass; mineralization; prevent; primary outcome; secondary outcome; sex; skeletal; transgender; young adult

PROJECT SUMMARY/ABSTRACT Access to and demand for gender-affirming medical therapy for gender non-conforming youth have increased, but understanding of the ramifications of these therapies on bone development and skeletal health has lagged behind. Current guidelines recommend treatment of gender dysphoria as early as Tanner Stage 2 with gonadotropin-releasing hormone agonists for puberty suppression, but little is known about the skeletal effects of this intervention. Puberty is a key period of skeletal vulnerability, as rapid longitudinal bone growth coupled with a lag in mass accrual results in decreased bone strength and increased fracture incidence. Peak bone mass, achieved during puberty and young adulthood, largely determines age-related fractures in later life. One European group has demonstrated attenuation of bone mineral density (BMD) accrual after pubertal suppression in older transgender adolescents that did not recover despite subsequent gender-affirming hormone therapy. Major determinants of bone health such as body composition, vitamin D status, weight- bearing exercise, and dietary calcium intake were not assessed. The skeletal effects of puberty suppression in early pubertal transgender youth have never been reported. The objective of this fellowship proposal is to examine measures of bone mass and quality during pubertal suppression in early pubertal transgender youth and to correlate these bone measures with major determinants of bone health. Dr. Lee has designed the proposed longitudinal observational cohort study, during which she will collect and analyze anthropometric, laboratory, and imaging data. We hypothesize that BMD, bone microarchitecture, and bone strength estimates will have attenuated accrual in early pubertal transgender youth after one year of pubertal suppression when compared to puberty-matched, non-transgender, control youth. Dr. Lee's proposed research to test this this hypothesis will concurrently provide training in the use and interpretation of pediatric bone densitometry (Aim 1) and high-resolution peripheral quantitative computed tomography (Aim 2). She will additionally perform complex longitudinal data analyses to determine the relationships between major determinants of skeletal development and bone mass, microarchitecture, and strength (Aim 3). These results will inform current clinical practices and lead to longer-term studies and investigations of interventions to mitigate the expected lag in skeletal development during pubertal suppression. Ultimately, this research will positively contribute to the clinical care of transgender youth. Dr. Lee is training to become a physician-scientist at the intersection of bone metabolism and gender- affirming therapy, a highly relevant area in need of rigorous investigation. Her mentorship team is comprised of experts in endocrinology, radiology, epidemiology, and biostatistics. They will ensure that Dr. Lee fulfills her training goals in advanced skeletal imaging, complex longitudinal data analysis, and the endocrinology of bone and transgender care, which will bolster her application for career development award.

项目概要/摘要 性别不合格青年获得性别肯定药物治疗的机会和需求已增加 增加但了解这些疗法对骨骼发育和骨骼健康的影响 已经落后了。目前的指南建议尽早在坦纳第二阶段治疗性别不安 用促性腺激素释放激素激动剂抑制青春期，但对骨骼的影响知之甚少 这种干预的效果。青春期是骨骼脆弱的关键时期，骨骼纵向生长迅速 再加上质量累积的滞后导致骨强度下降和骨折发生率增加。顶峰 青春期和成年早期达到的骨量在很大程度上决定了晚年与年龄相关的骨折。 一个欧洲研究小组已证明青春期后骨矿物质密度 (BMD) 的增加会减弱 尽管随后进行了性别肯定，但年龄较大的跨性别青少年仍没有康复 激素疗法。骨骼健康的主要决定因素，如身体成分、维生素 D 状况、体重 没有评估承受运动和膳食钙摄入量。青春期抑制对骨骼的影响 青春期早期变性青年从未有过报道。该研究金提案的目的是 检查青春期早期青春期抑制期间骨量和骨质量的测量 跨性别青年，并将这些骨骼测量值与骨骼健康的主要决定因素联系起来。博士。 Lee 设计了拟议的纵向观察队列研究，在此期间她将收集和 分析人体测量、实验室和成像数据。我们假设 BMD（骨微结构） 青春期早期跨性别青年的骨强度估计值将在一年后减弱 与青春期匹配的非跨性别对照青少年相比，青春期抑制的年份。博士。 李提出的测试这一假设的研究将同时提供使用和使用方面的培训 儿科骨密度测定（目标 1）和高分辨率外周定量计算的解释 断层扫描（目标 2）。她还将进行复杂的纵向数据分析，以确定 骨骼发育的主要决定因素与骨量、微结构和骨量之间的关系 强度（目标 3）。这些结果将为当前的临床实践提供信息，并导致长期研究和 对缓解青春期骨骼发育预期滞后的干预措施进行调查 抑制。最终，这项研究将为跨性别青少年的临床护理做出积极贡献。 李博士正在接受培训，成为一名骨代谢和性别交叉领域的医师科学家。 肯定疗法是一个高度相关的领域，需要严格的研究。她的导师团队包括 内分泌学、放射学、流行病学和生物统计学专家。他们将确保李博士满足她的要求 高级骨骼成像、复杂纵向数据分析和骨内分泌学的培训目标 和跨性别关怀，这将有助于她申请职业发展奖。